Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: A study in Chinese patients with very small nodules

Chen Chen, Xiaojie Huang, Wei Yin, Muyun Peng, Fang Wu, Xia Wu, Jingqun Tang, Mingjiu Chen, Xiang Wang, Alicia Hulbert, Malcolm V. Brock, Wenliang Liu, James G. Herman, Fenglei Yu

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Abstract

Purpose: We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples. Experimental design: Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP. Results: Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41-69% and 49-82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84-0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm. Conclusions: Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Article number828
JournalClinical Epigenetics
Volume12
Issue number1
DOIs
StatePublished - Mar 5 2020

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Keywords

  • Biomarker
  • DNA methylation
  • Early detection
  • Lung cancer
  • Plasma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Chen, C., Huang, X., Yin, W., Peng, M., Wu, F., Wu, X., Tang, J., Chen, M., Wang, X., Hulbert, A., Brock, M. V., Liu, W., Herman, J. G., & Yu, F. (2020). Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: A study in Chinese patients with very small nodules. Clinical Epigenetics, 12(1), [828]. https://doi.org/10.1186/s13148-020-00828-2